Share this:

Award Ceremony Speech

Presentation Speech by Professor E.
Hammarsten, member of the Staff of Professors of the Royal Caroline Institute,
on December 10, 1937

Your Majesty, Your Royal Highnesses, Ladies
and Gentlemen.

The Staff of Professors of the Caroline Institute, pursuant to
the task devolving upon them by the terms of the will of Alfred
Nobel, have awarded the Prize for Physiology or Medicine for the
year 1937 to Professor Albert von Szent-Györgyi, in
recognition of his discoveries concerning the biological
combustion processes with especial reference to vitamin C and
to the fumaric acid catalyst. The wording of the above sentence
indicates that the mechanism of biological oxidation has been
investigated beyond the great discoveries in this field made by
Otto Warburg, Heinrich Wieland, and
their successors. Their systems of catalysts for oxidation have
been shown to be dependent on Szent-Györgyi's new
catalysts.

It was generally known before that combustion liberates energy in
living cells which can be employed there without loss - directly
for the building up of new substances - for storage or for the
building of functioning cell structures. The building up of
living organisms then is dependent in essential respects on
combustion, which is guided by catalyst systems. Thus catalyst
systems are conditional for the building up of living organisms.
Consequently in the unknown period during which organic life
originated, the formation of these and other catalyst systems
must have preceded the completion of the living animal
organisms.

Preferably I should wish to confine my remarks to the new
conquistador from Szeged. The survey is however of higher
importance on this occasion, and moreover the course of the
events is dramatically concentrated. Each one of the three has
conquered new ground by intuitive daring and skill.
Szent-Györgyi's greatest achievement has intimately linked
up the accomplishments of the two others and of their successors,
giving us for the first time a picture of a coherent oxidation
process - of the interplay of three catalyst systems and the
oxidation thereby in metabolism.

Warburg, who always stood alone with some few faithful
co-workers, is the foremost pioneer, and he had to overcome the
greatest difficulties. At this day there is none who can any
longer throw doubt on his discoveries, but that was not so, when
in 1931 underestimated by the majority, he was awarded the Nobel
Prize by the Caroline Institute. He has shown that the inert
oxygen, with which the red blood corpuscles are fully loaded, is
taken up from them by a catalyst system to which many red
pigments belong (for brevity's sake called «the red
system»). These are related to the red blood pigment. They
contain as active groups (for the most part) iron and specific
proteins. In this system the oxygen combines with the iron during
varying periods of time. In the case of the most rapid catalysts,
it combines with the iron, is converted into a lively, reactively
disposed form and is delivered - all at a speed that gives a
flowing stream of active oxygen from the catalyst system. One
thought that this active oxygen oxidized directly. That is not
the way however. On the contrary, the active oxygen meets
hydrogen - but that is another story, belonging to
Szent-Györgyi's great discovery. The manner in which the
life-giving active oxygen's dramatic encounter in the darkness of
the cells ensues, had been unknown ever since the morning of time
until, in 1933, Szent-Györgyi carried out some experiments
which proved to be the prelude to the revelation of the
secret.

For the moment I will leave oxygen, and direct the attention to
the first, apparently unimportant, experiments carried out by
Wieland. These led him to the conception of an idea, which was
destined to carry him on to the disclosure of an extensive part
of the mechanism of oxidation. A large number of investigators
were soon attracted by Wieland's opinion. This seemed to be at
variance with the oxygen activation - at any rate that was the
view of a majority. This apparent inconsistency was never
considered by Szent-Györgyi, nor by Warburg.

Wieland had observed that palladium is capable of absorbing
hydrogen from certain organic compounds, which means their
partial combustion or oxidation. Through the cooperation of many
investigators the presence was revealed of extensive metal-free
catalyst systems, the effect of which was shown to consist in the
removal of hydrogen from metabolic substances, in agreement with
Wieland's concept. These catalysts were given a name in common:
dehydrogenases (hydrogen-removers, hydrogen-absorbers, or
hydrogen-transporters) and the idea was held pretty generally
that the hydrogen activated by this system would be capable of
reacting directly with the inert oxygen molecules. Hydrogen
superoxide was supposed to form an intermediate product. That is
not the highway of oxidation however. On the contrary, the
hydrogen first meets Szent-Györgyi's catalyst system from a
different side to the one where the activated oxygen flows into
it from the «red system». That again is another story,
which also belongs to Szent-Györgyi's great discovery. From
1925 onwards he had been investigating a number of
hydrogen-absorbers. Previously to anyone else he formed the view
of these as members of a catalyst system in the service of
oxidation (in other quarters loosely conceived of as being
auxiliary catalysts of some kind for fermentation). He was also
occupied with experiments on a yellow substance, termed
flave by him, while his investigation regarding vitamin C
was being completed, and conducted on to the isolation of that
substance, enabling him later to insert it in the catalyst system
of certain hydrogen-removers. Vitamin C and another substance,
containing sulphur as a hydrogen-removing group and defined by
Sir Frederick Gowland Hopkins
and others, were however until 1934 the only substances belonging
to the hydrogen-transporters in the oxidation-chain that had been
isolated. The rank that they possess as catalysts is dependent on
the velocity of the hydrogen-transportation and the degree of the
activation of the hydrogen - problems that still await a
satisfactory solution. On the other hand, Hugo Theorell succeeded in 1934 in
isolating, in Warburg's laboratory, the first really rapid
hydrogen-transporter, called «the yellow enzyme». He
could also show that it was a phosphoric-acid ester of vitamin
B2, linked to a specific protein. Warburg and
Christian, in 1935, defined the nature of the active group in two
other dehydrogenases, colourless and metal-free (co-ferment and
co-zymase), which had long frustrated the attempts of other
investigators. One of them was the catalyst that
Szent-Györgyi had placed in this section of the
oxidation-chain.

The magnificent series of Szent-Györgyi's discoveries
commenced in 1933. They were carried out and pursued at Szeged
with extraordinary rapidity and precision. His clear vision for
essentials induced him, in spite of his isolation of ascorbic
acid and of his identification of it with the so-termed
vitamin C - a feat that was justly hailed with enthusiasm - to
hand over to others for the time being the tempting pursuit of
the further development of that discovery, and to devote the
whole of his energy to the problem of combustion, notwithstanding
the difficulties it presented. Many investigators had been
working at the so-called plant acids in the muscular system, and
had observed their capacity for intensifying oxidation in that
tissue. The readiest explanation however of how that came about,
viz. that they are easily combusted themselves, simply did not
fit in with Szent-Györgyi's intuitive perception. By
elaborating reliable methods of analysis for the substances in
question, and by means of consistent experiments, he and his
co-workers proved that the plant acids were not consumed by
combustion, were not ordinary nutrient substances, but were on
the contrary themselves active groups of catalysts which served
to maintain the combustion without themselves suffering any
diminution thereby. The process involves a peregrination of
hydrogen more intricate than the adventurous journeys of
Odysseus, though more rapid. Hydrogen is released out of the
metabolic substances, probably through cooperation between
Szent-Györgyi's and Warburg's co-ferment and Theorell's
yellow enzyme, and encounters the plant acids, entering in that
way Szent-Györgyi's's system. These acids transfer the
system into the order: oxalacetic acid, malic acid, fumaric acid,
and succinic acid, then, in the form of active hydrogen, to
encounter the active oxygen from «the red system» and
form water and free energy - a series of providentially subdued
explosions which I alluded to before as a dramatic encounter. The
plant acids act as catalysts by cooperation with specific
proteins, and the effect of the yellow enzyme probably extends
some way into this Szent-Györgyi's intermediate
system.

Thus, the oxygen-activation in the red iron system and
hydrogen-transfer from nutrients by the yellow metal-free system
along with co-agents have been united by Szent-Györgyi
through the discovery of this intermediate system. The interplay
of «the red system»'s cytochrome-group and the yellow
enzyme might probably also, according to Theorell, proceed
directly. The flaws are numerous, but not of a character to
constitute any essential breach in the highway of the
oxidation-chain. Numerous ramifications of the latter however
already begin to be discernible.

It is of especially great importance that at least two vitamins -
C and B2, and possibly B1, and P - are in
cooperation in the oxidation chain and are catalysts,
illustrating the way in which these vitamins act in the organism.
It may be that development in the near future will reveal the
importance for our organism of copper concerning oxidation and of
vitamin C with certain followers in plants, viz. oxidating
enzyme, and oxidizable and reducible substances
(Szent-Györgyi's flavonoles, termed vitamin P), which are
capable of forming a sensitively attuned system with the vitamin,
hydrogen-superoxide and proteins, or parts of them, with active
and activating sulphur in the molecule. The sulphur of the
alchemists of old, out of which everything was to radiate, is
destined to experience a renaissance.

Professor Albert von Szent-Györgyi. As
a representative for the Caroline Institute on this occasion, I
am commissioned to give expression to our high estimation of your
researches.

You never swerved from your unyielding purpose to study the
primary and fundamental processes of biological oxidation.
Entering upon this difficult field of biochemical research you
soon became a pioneer by interpreting the position and real
function of co-ferment as an important link in the chain of
dehydrogenating catalysts. Not even your important discoveries
regarding vitamin C could deter you from following a certain
strain of thought. I am deducing now from a close observation of
your work that you were drawing distinctions in your mind at this
occasion between your interesting discovery of ascorbic acid and
the bare possibility of some other audacious plans of yours
coming true. At this early stage they must have involved the
investigation of the fundamental mechanism of connecting hydrogen
activation with that of oxygen activation. Your intuitive mind
decided in favour of the possibility of success, and you won
through. In the year 1933 the first signs became visible for
outsiders, and from then on the pace set by you and your
co-workers at Szeged was astonishing, and your results were
fundamentally new and highly important. In the midst of fervent
research work with most promising aspects you are the discoverer
and idealist to the mind of Alfred Nobel.

I ask you, Professor Szent-Györgyi, to receive the prize
from the hands of His Majesty, our gracious King.